Individual and combined haematotoxic effects of fumonisin B1 and T-2 mycotoxins in rabbits

Szabó, András; Szabó-Fodor, Judit; Fébel, Hedvig; Romvári, Róbert; Kovács, Melinda

doi:10.1016/j.fct.2014.07.025

Cited by 25 publications

(19 citation statements)

References 37 publications

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“…Their mode of toxic action is rather divergent, as the inhibition of protein synthesis (specifically in eukaryotes) and inhibition of DNA synthesis (9), or the disruption of the mitochondrial electron transport system (26), augmented lipid peroxidation, affecting ultimately cell membrane integrity. According to Ngampongsa et al's study (26), the ATPlinked oxygen consumption rate of cardiomyocyte mitochondria is compromised by T-2 toxin, which is underpinned with our recent results, in which rabbit erythrocyte Na + /K + ATPase activity (the rate of ATP breakdown) was markedly lowered by T-2 toxin (33). It was established that in the rat liver, T-2 toxin inhibits the mitochondrial electron transport system, concluding that mitochondria are possible hepatic targets of T-2 toxin action (27).…”

Section: Introductionmentioning

confidence: 68%

“…In our earlier study (33), in the erythrocyte membrane, oleic acid provided the highest proportion in the combined treatment. This partly agrees with the results of Gelderblom et al (17), who reported that FB 1 at 100 mg/kg feed induced delta-9 desaturase activation and increased membrane monounsaturation.…”

Section: Liver Mitochondrial Phospholipidsmentioning

confidence: 99%

“…In our recent study, it was found that at levels of 2 mg/kg diet T-2 toxin alone, or 10 mg/kg diet fumonisin B 1 (FB 1 ) alone, and both toxins in combination exerted hepatotoxic effect and acted antagonistically onto the red cell sodium pump ATP breakdown capacity, T-2 markedly lowering its activity (33). However, red cell membrane fatty acyl chain composition was only slightly modified in the cells of the systemic circulation, supposing that both toxins act at the level of polychromatic erythroblasts.…”

Section: Introductionmentioning

confidence: 99%

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Oral administration of fumonisin B₁and T-2 individually and in combination affects hepatic total and mitochondrial membrane lipid profile of rabbits

Szabó¹,

Szabó-Fodor²,

Fébel³

et al. 2016

Physiology International

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Weaned rabbits were fed diets contaminated with 2 mg/kg diet T-2 toxin alone, or 10 mg/kg diet fumonisin B 1 (FB 1 ) alone, and both toxins in combination (2 + 10 mg/kg, respectively) compared to a toxin-free control diet. Samplings were performed after 4 weeks (blood and liver). Bodyweight of T-2-fed group was lower after 4 weeks; the liver weight was increased dramatically (threefold of control). Liver total phospholipids (PLs) provided slight alterations in the fatty acid (FA) composition; all three toxin-treated groups showed a decrease in palmitoleic acid (C16:1 n7) proportion. In the liver mitochondrial PL FA composition, margaric acid (C17:0) proportion decreased in the separated toxin treatments compared to the combined setting. Oleic acid (C18:1 n9) proportion was increased and arachidonic acid (C20:4 n6) was decreased in the FB 1 -treated group, while docosapentaenoic acid (C22:5 n3) was decreased in the separated treatments. The total monounsaturation was significantly higher in the FB 1 group's mitochondrial PL FA profile. After 4 weeks, all toxin treatments decreased the blood plasma reduced glutathione and glutathione peroxidase activity, and FB 1 increased the plasma sphinganine/sphingosine ratio. Both mycotoxins seem to cross the hepatocellular and the hepatic mitochondrial membrane, without drastic membrane disruption, as assessed from the PL FA composition, but inducing detectable lipid peroxidation.

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Section: Introductionmentioning

confidence: 68%

Section: Liver Mitochondrial Phospholipidsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Oral administration of fumonisin B₁and T-2 individually and in combination affects hepatic total and mitochondrial membrane lipid profile of rabbits

Szabó¹,

Szabó-Fodor²,

Fébel³

et al. 2016

Physiology International

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“…As rats perform coprophagy, they ingest bacterial fatty acids which are then incorporated into their glycerolipids. It is important to note that in rabbits (performing caecotrophy) the red cell membrane (Szabó et al, 2014) and the hepatic mitochondrial membrane showed identical changes as a result of 10 mg/kg feed FB 1 exposure for 28 days. It might be thus assumed that in rodents the lowered cell membrane margaric acid proportion (induced by FB 1 toxin exposure) contributed to the increase of membrane fluidity, as a means of counterbalancing the proportional decrease of the much more fluid polyunsaturated FAs (C22 PUFAs).…”

Section: Fatty Acid Composition Of Hepatic Phospholipidsmentioning

confidence: 99%

Acute hepatic effects of low-dose fumonisin B1 in rats

Szabó

Szabó-Fodor

Fébel

et al. 2016

Acta Veterinaria Hungarica

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Adult male Wistar rats were enrolled in a study to test the acute hepatic effects of 50 mg/kg fumonisin B 1 in feed for 5 days. Fumonisin B 1 depressed growth and feed intake, and absolute and relative liver weight showed a significant increase. The proportions of C17:0, C18:3 n3, C22:5 n3 and C22:6 n3 fatty acids decreased in the hepatic phospholipid fraction. All proportional decreases modified the hepatocellular membrane lipids into a more rigid state. The fatty acid profile modifications were partly compensated for by endogenous glutathione (preventing the formation of conjugated dienes and trienes as initial phase lipid peroxidation indicators), while the enzymatic antioxidant defence system (glutathione peroxidase) was unaltered. In contrast, hepatic malondialdehyde, the cytotoxic product of end-phase lipid peroxidation showed a concentration increase even after 5 days of feeding. The results indicate a rather strong and rapid hepatic effect of FB 1 , immediately impairing membrane phospholipids, even before the enzymatic antioxidant defence is activated.Key words: Fumonisin B 1 , rat, hepatocellular membrane, fatty acids, oxidative stress, antioxidants Fumonisins are cancer-inducing metabolites of Fusarium proliferatum and Fusarium verticillioides. They have a long-chain hydrocarbon unit (mimicking to a certain extent cellular sphingosine and sphinganine), which plays a determinant role in their cell-membrane-associated toxicity. From the fumonisin group, fumonisin B 1 (FB 1 ) shows strong toxic effects and has been reported to promote hepatic tumour in rats. Fumonisin B 1 , the most abundant of the numerous fumonisin analogues, was classified by the IARC as a Group 2B carcinogen (possibly carcinogenic in humans; IARC, 2002).

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“…Another study carried out by Szabó et al (2014), investigating red blood cell Na + / K + ATPase activity in weaned rabbits, found antagonism between the two toxins. The present study investigates the individual and combined effects of subclinical doses of FB 1 and T-2 on feed intake, body weight, DNA damage, histopathology, serum biochemistry and antioxidant capacity in weaned rabbits.…”

Section: Introductionmentioning

confidence: 99%

Individual and combined effects of feed artificially contaminated with with fumonisin B1 and T-2 toxin in weaned rabbits

Hafner

Szabó

D’Costa

et al. 2016

WMJ

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Co-contamination of feed and feed raw materials with two or more mycotoxins is frequently reported, however, only a few studies have investigated the combined effects of low doses of multiple mycotoxins. In the present study the individual and combined effects of 10 mg/kg fumonisin B 1 and 2 mg/kg T-2 toxin (n=12/group) were investigated in weaned rabbits. Mycotoxin contaminated feed was produced by adding fungal cultures of Fusarium verticillioides and Fusarium sporotrichioides, and fed to 40 days old rabbits during 28 days. Feed intake and body weight were measured weekly, serum biochemistry and antioxidant parameters on day 0, 14 and 28, while histopathological examination and comet assay were performed at the end of the experiment. T-2 exposure both alone and in combination resulted in 15-18% less final body weight compared to the control and FB 1 treatment. There was a significant increase in the concentration of plasma total protein, albumin, fructosamine and creatinine in the group treated with FB 1 compared to the control. The liver and the kidney of most animals treated with T-2 toxin, FB 1 and their combination showed pathological changes, occurring more frequent in animals exposed to both toxins. T-2 resulted in depletion of lymphocytes in the spleen. FB 1 and T-2 exerted synergistic effect on the antioxidant/oxidative parameters after 2 weeks of exposure, manifesting in less glutathione and glutathione peroxidase, while more malondialdehyde was produced. Both toxins caused DNA damage in the lymphocytes, which was more pronounced in the group fed T-2 toxin and T-2 combined with FB 1 , without additive or synergistic effects.

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Individual and combined haematotoxic effects of fumonisin B1 and T-2 mycotoxins in rabbits

Cited by 25 publications

References 37 publications

Oral administration of fumonisin B₁and T-2 individually and in combination affects hepatic total and mitochondrial membrane lipid profile of rabbits

Oral administration of fumonisin B₁and T-2 individually and in combination affects hepatic total and mitochondrial membrane lipid profile of rabbits

Acute hepatic effects of low-dose fumonisin B1 in rats

Individual and combined effects of feed artificially contaminated with with fumonisin B1 and T-2 toxin in weaned rabbits

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Individual and combined haematotoxic effects of fumonisin B1 and T-2 mycotoxins in rabbits

Cited by 25 publications

References 37 publications

Oral administration of fumonisin B1and T-2 individually and in combination affects hepatic total and mitochondrial membrane lipid profile of rabbits

Oral administration of fumonisin B1and T-2 individually and in combination affects hepatic total and mitochondrial membrane lipid profile of rabbits

Acute hepatic effects of low-dose fumonisin B1 in rats

Individual and combined effects of feed artificially contaminated with with fumonisin B1 and T-2 toxin in weaned rabbits

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Oral administration of fumonisin B₁and T-2 individually and in combination affects hepatic total and mitochondrial membrane lipid profile of rabbits

Oral administration of fumonisin B₁and T-2 individually and in combination affects hepatic total and mitochondrial membrane lipid profile of rabbits